NM_000202.8(IDS):c.1300G>A (p.Glu434Lys) AND Mucopolysaccharidosis, MPS-II

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 7, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002467471.3

Allele description [Variation Report for NM_000202.8(IDS):c.1300G>A (p.Glu434Lys)]

NM_000202.8(IDS):c.1300G>A (p.Glu434Lys)

Gene:

IDS:iduronate 2-sulfatase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000202.8(IDS):c.1300G>A (p.Glu434Lys)

HGVS:

NC_000023.11:g.149483099C>T
NG_011900.3:g.27236G>A
NM_000202.8:c.1300G>AMANE SELECT
NM_001166550.4:c.1030G>A
NP_000193.1:p.Glu434Lys
NP_001160022.1:p.Glu344Lys
NC_000023.10:g.148564630C>T

Protein change:

E344K

Molecular consequence:

NM_000202.8:c.1300G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001166550.4:c.1030G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-II (MPS2)
Synonyms:: Mucopolysaccharidosis type II; Attenuated MPS (subtype; formerly known as mild MPS II); Severe MPS II; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010674; MedGen: C0026705; Orphanet: 580; OMIM: 309900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002754412	Serv. Biochemistry and Molecular genetics, Hospital Clinic de Barcelona, Hospital Clínic de Barcelona	no assertion criteria provided	Pathogenic (Nov 23, 2022)	maternal, not applicable	research, in vitro
SCV005089520	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 7, 2024)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 9875019, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002754412

Serv. Biochemistry and Molecular genetics, Hospital Clinic de Barcelona, Hospital Clínic de Barcelona

no assertion criteria provided

Pathogenic
(Nov 23, 2022)

maternal, not applicable

research, in vitro

SCV005089520

Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 7, 2024)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro
not provided	germline	yes	1	not provided	not provided	not provided	not provided	literature only
not provided	maternal	yes	2	1	not provided	not provided	not provided	research

Citations

PubMed

Mutation analysis in 57 unrelated patients with MPS II (Hunter's disease).

Vafiadaki E, Cooper A, Heptinstall LE, Hatton CE, Thornley M, Wraith JE.

Arch Dis Child. 1998 Sep;79(3):237-41.

PubMed [citation]

PMID:: 9875019
PMCID:: PMC1717680

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Serv. Biochemistry and Molecular genetics, Hospital Clinic de Barcelona, Hospital Clínic de Barcelona, SCV002754412.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	research	not provided
2	not provided	not provided	not provided	not provided	in vitro	not provided

Description

There are two brothers affected. They both are hemizygous for the variant reported here, and their mother is a carrier.

Description

The c.1300G>A (p.Glu434Lys) was detected in hemizygosity in two affected brothers. The mother was a carrier of the variant. The two boys showed excretion of dermatan and heparant in urine, both show clinical phenotype of MPS II. In the lab we analysed the iduronate-2-sulfatase activity in blood spots and it was 0,6 micromol/Lxh (control range 3.2-8.6). Because of these reasons we consider the variant as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided		2	not provided	1	not provided
2	not applicable	not applicable	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV005089520.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (2)

Description

Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Strong)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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